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Biomedical subjects

T Menzel

Publications and source records attributed to T Menzel.

At least 55 records · Page 3Linked to original sources

[Single right coronary artery with absence of the left coronary ostium].

We report the rare congenital anomaly of a singular right coronary artery in absence of the left coronary ostium. In a 31-years-old man, coronary arterial angiography demonstrated a right coronary artery which, arising from the right Sinus Valsalvae, first described the normal right coronary arterial course but in the apical region continued to follow, in reverse direction, the normal course of the left anterior descending artery. The proximal diameter of the vessel measured 5.2 mm. Thallium scintigraphy showed no ischemia of the anterior wall. The risk of developing circumscribed atherosclerosis due to anatomical reasons seems not to be increased, as no additional bifurcation nor kinking was to be found.

Adult↗

In vivo time and dose dependency of interleukin-6 secretion in response to low-dose subcutaneous recombinant interleukin-2.

Serum concentrations of Interleukin-6 (IL-6) were determined in renal cell carcinoma patients treated with low-dose subcutaneous human recombinant interleukin-2 (rIL-2). In all patients, administration of rIL-2 resulted in a significant increase in IL-6 serum levels to peak values within 4 to 6 hours as measured by enzyme-linked immunosorbent assays (ELISA). Repetitive administration of rIL-2 induced significantly lower IL-6 serum peaks when compared to the initial administration of rIL-2. Cumulative IL-6 release, as expressed by the area under the concentration curve (AUC), appeared to be independent of rIL-2 dose distribution (10 million IU rIL-2/m2 versus 20 million IU rIL-2/m2), and IL-6 serum peaks showed no direct dose dependency. Prior rIL-2 immunotherapy had no measurable effect on rIL-2 induced IL-6 release, while steroids resulted in a significant suppression of secondary IL-6 did not correlate with response to rIL-2 therapy or survival of rIL-2 treated renal cell carcinoma patients.

Aged↗

Hepatic and serologic toxicity of systemic interleukin-2 and/or interferon-alpha. Evidence of a risk-benefit advantage of subcutaneous therapy.

A total of 107 cancer patients were treated with 148 cycles of subcutaneous (SC) immunotherapy employing interleukin-2 (rIL-2) and/or interferon-alpha (rIFN-alpha). The systemic toxicities of SC cytokine therapy were retrospectively evaluated with regard to hepatic and metabolic adverse effects, and compared to adverse effects previously reported upon high- or intermediate-dose intravenous (IV) rIL-2 therapy. Our study cohorts consisted of 15 patients who received SC rIL-2 at doses of 4.8-14.4 million IU/m2/day on 5 days per week for a total of 8 weeks, 20 patients who received rIFN-alpha 2b at 3.0-6.0 million U/m2/day thrice weekly for a total of 6 weeks, and 72 patients who were given SC rIFN-alpha 2b at 6.0 million U/m2/day thrice weekly plus SC rIL-2 at 14.4-18.0 million IU/m2/day on days 1 and 2, followed by 4.8 million IU/m2/day, 5 days per week for 6 consecutive weeks. These treatment regimens were well tolerated in the outpatient setting; no toxic deaths occurred, and none of the patients developed life-threatening toxicity. Upon SC rIL-2/rIFN-alpha combination therapy, we observed mild decreases in plasma protein and albumin levels (mean nadir +/- standard deviation, 67 +/- 5 g/L and 38.8 +/- 3.9 g/L, respectively), minor albeit significant increases in serum total bilirubin levels (mean peak +/- standard deviation, 7.8 +/- 3.1 mumol/L), serum aspartate aminotransferase (25.9 +/- 9.9 U/L), alanine aminotransferase (42.0 +/- 45.9 U/L), alkaline phosphatase (301 +/- 255 U/L), lactate dehydrogenase (230 +/- 64 U/L), gamma-glutamyl transpeptidase (147 +/- 141 U/L) activities and triacylglyceride (2.6 +/- 0.9 mmol/L) concentrations. Cholinesterase activities (mean nadir +/- standard deviation, 42.6 +/- 13.7 kU/L), and serum cholesterol levels (4.4 +/- 0.9 mmol/L) decreased upon SC rIL-2/rIFN-alpha combination therapy. These mild clinical side effects and laboratory changes were in marked contrast to a multitude of dose-limiting and life-threatening adverse reactions described upon IV rIL-2 therapy. It is concluded that low-to intermediate-dose SC rIL-2/rIFN-alpha combination therapy as used in this study, can be given in the outpatient setting with good practicability and excellent safety.

Adult↗

[Comparison of conventional and miniaturized biplane echoscope: initial clinical results].

A subset of patients experiences substantial discomfort on examination with transesophageal echocardiography using the conventional echoscope, whereby the dimensions of the probe play a decisive role. Miniaturized biplane transducers have recently become available (2 x 32 crystals; dimensions 9.5 x 8.7 mm; circumference approx. 30% less than the conventional echoscope), which allow ultrasound examination at 3.5, 5.0 and 7.0 MHz. A prospective study was carried out in 70 patients to compare difficulties on insertion of the probe, subjective evaluation by the patient during examination, and the 2D-image as well as Doppler and color-coded Doppler quality of the miniaturized biplane echoscope. In 43 patients, intubation of the esophagus proved less difficult with the smaller instrument, it was more difficult in 8 cases. 54 patients reported that the discomfort was definitely easier to bear on use of the narrow instrument. Concomitant parasympathicolytic medication was needed with the smaller probe in 4 cases, and 11 times with the conventional echoscope. The quality of the 2D-image attained by the miniaturized probe was naturally lower. Employing multi-Hertz technology at a frequency of 7 MHz, however, imaging of the anatomy was excellent in the near field of 5-6 cm, and nearly equivalent to that of the conventional probe (5 MHz). The quality of PW-and CW-Doppler as well as color-coded Doppler information was identical. Whenever examination with a conventional echoscope promises to be difficult, or when sedation is contraindicated due to a severe illness or respiratory insufficiency, transesophageal echocardiography should be considered with a smaller biplane probe at higher frequencies.

Adolescent↗

[Partial anomalous pulmonary venous return--detection of an isolated aberrant right upper pulmonary vein into the superior vena cava with biplanar transesophageal echocardiography].

We report on a case of partial anomalous pulmonary venous return in a patient (54 years old, female) examined for the cause of pulmonary hypertension. Biplane transesophageal echocardiography in conjunction with color-coded ultrasound technique revealed an aberrant vessel draining into the vena cava superior. The PW-Doppler pattern typical of venous flow and a lack of the upper right pulmonary vein connection into the left atrium allowed identification with the pulmonary venous system. This malconnection was not accompanied by associated anomalies, or defects of the atrial septum in particular. Invasive examination confirmed the echocardiographic results; with an angiographic catheter the opening of the right upper pulmonary vein into the superior vena cava was located exactly and depicted.

Blood Flow Velocity↗

Lack of therapeutic efficacy of tamoxifen in advanced renal cell carcinoma.

In the present study, we treated a total of 62 patients with advanced renal cell carcinoma with high-dose tamoxifen (100 mg/m2/day). Patients were treated in the outpatient setting, and were evaluated 8-12 weeks after initiation of therapy or sooner, when clinical disease progression was evident; a total of 15 patients were seen at short regular intervals for evaluation of clinical and laboratory parameters. Of these 62 patients, 59 were evaluable for treatment response, survival and systemic toxicity. One partial remission was achieved (1.7%; 95% confidence interval, 0.04-9.09%), response duration was 3 months. 10 patients presented with stable disease, for a median duration of 4.0 months, and 48 patients exhibited disease progression upon and after therapy. Systemic toxicity was significant; severe fatigue occurred in 5% of patients, and moderate anaemia, dyspnea, alopecia and malaise in almost 20% of patients. Antineoplastic efficacy of tamoxifen at this dosage in this cohort of patients was at best marginal and well in the range associated with the occurrence of spontaneous remissions. Toxicity was substantial, and it was not balanced by therapeutic benefit. This is consistent with the known lack of therapeutic efficacy of endocrine therapy in advanced renal cell carcinoma.

Adult↗

Clinical and preclinical evaluation of recombinant PEG-IL-2 in human.

High dose interleukin-2 alone or in combination with lymphokine activated killer (LAK) cells has demonstrated antitumor activity in a variety of malignant diseases. The currently formulated recombinant human interleukin-2 (IL-2) has limited solubility and short circulatory half life resulting in limited bioavailability. To improve the bioavailability of IL-2 the protein was covalently bound to activated Polyethylenglycol (PEG). We designed a phase I/II trial to evaluate the bioactivity of PEG-IL-2 in man, given as intravenous (iv) bolus injection every two weeks, and to determine safety, efficacy, and the maximum tolerated dose (MTD) in patients with advanced malignancies. Assessment of cytokine levels, phenotypic analyses and differential blood counts were performed to investigate the effects of PEG-IL-2 in-vivo. To compare in-vitro PEG-IL-2 activity to activities of IL-2 we evaluated proliferation, cytotolytic activity, morphology, and phenotype of cytokine activated lymphocytes. Among seven patients treated with PEG-IL-2, there was no objective remission, three patients exhibited stabilisation of disease. Four patients presented with further disease progression. Treatment-related toxicity was mild to moderate (mainly WHO grades I and II) in patients receiving dose levels up to 10 x 10(6) IU/m2 (maximum tolerated single dose in the outpatient setting). No toxic deaths occurred. In comparison to IL-2, the pharmacokinetic profile of PEG-IL-2 exhibited increased plasma levels and a decreased clearance (alpha and beta half-life estimates of 4 and 14 hours, respectively). The analysis of a variety of immunologic parameters demonstrated that PEG-IL-2 has significant biologic activity both in vitro, and in man.

Adult↗

Limited efficacy of interferon-alpha and vinblastine as second line biochemotherapy regimen in patients with progressive metastatic renal cell carcinoma.

We report on thirty-four patients with metastatic renal cell carcinoma who were treated with a combination of subcutaneous recombinant interferon-alpha and intravenous vinblastine upon progression after previous antineoplastic therapy. Pretreatment included chemotherapy (n = 3), hormonal therapy (n = 6) and immunotherapy (interleukin-2/interferon-alpha, n = 25). In this study, treatment courses consisted of subcutaneous doses thrice weekly of recombinant interferon-alpha at 6 million U/m2 (20 patients, group 2), respectively. Treatment was given over 8 consecutive weeks. Additionally, in all patients, vinblastine was administered intravenously at a dose of 6 mg/m2 in weeks 2, 5 and 8. Of 14 patients treated in group 1, one had a partial response for 6 months (overall response rate 7.14%; 95% confidence interval, 0.18-33.87%), and four had disease stabilization (median duration, 5.0 months). Of 20 patients treated in group 2, there was one patient who achieved a complete response (response duration, 34+ months); in addition, two patients had a partial response (median response duration, 10.5+ months; overall response rate, 15%; 95% confidence interval 3.21-37.89%), and 13 patients exhibited disease stabilization (median duration 5.9+ months). Response rates showed no significant differences when comparing treatment results in patients in group 1 vs group 2. In contrast, significantly less patients treated in group 2 had progressive disease (p = 0.024), as compared to patients in group 1. This treatment combination was overall well tolerated with low to moderate systemic toxicity. In addition, there were no significant differences in frequency or intensity of therapy-related systemic toxicities when comparing patients in group 1 and group 2, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Low-dose interleukin-2 in combination with interferon-alpha effectively modulates biological response in vivo.

Phenotypic characterization of peripheral blood lymphocytes was performed in patients with advanced metastatic cancer receiving low-dose recombinant interleukin-2 (rIL-2) and recombinant interferon-alpha (rIFN-alpha) as subcutaneous home therapy. A total of 31 patients with progressive metastatic renal cell carcinoma, malignant melanoma, colorectal cancer, B-cell lymphoma, and Hodgkin's disease, were evaluated. Patients were treated with a combination of low-dose subcutaneous rIL-2 and rIFN-alpha, consisting of a 2-day rIL-2 pulse at 9.0 million IU/m2 twice daily, followed by 6 weeks of combined low-dose rIL-2 at 1.8 million IU/m2 twice daily, 5 days per week, and rIFN-alpha at 5.0 million U/m2 3 times per week. This treatment regimen resulted in an overall significant (p < 0.002) increase in peripheral blood lymphocyte subsets expressing CD3, CD8, CD16, CD25, and CD56. Expansion of peripheral blood natural killer (NK) cells was correlated to treatment response. Thus, treatment-related increase in CD56-positive lymphocytes was 1.8-fold higher in complete or partial responders when compared to progressive disease patients (p = 0.0). Increase in NK cells upon low-dose rIL-2 and rIFN-alpha was associated with a significant expansion (p = 0.0) of peripheral blood eosinophils (r = 0.71). Patient pretreatment using rIL-2, rIL-2 and rIFN-alpha, or chemotherapy abrogated the treatment-induced induction of NK cells and IL-2 receptor- (CD25) positive T lymphocytes, respectively. Peripheral blood NK cells were significantly decreased (p < 0.05) in patients developing neutralizing antibodies specific to rIL-2.

Antibodies↗

Expansion of peripheral blood natural killer cells correlates with clinical outcome in cancer patients receiving recombinant subcutaneous interleukin-2 and interferon-alpha-2.

Natural killer (NK) cells are believed to contribute to the clinical efficacy of cancer immunotherapy using recombinant interleukin-2 (rIL-2) in humans. In previous trials of high-dose i.v. rIL-2, however, no correlation has been established between circulating NK cells and treatment response. Between January 1989 and October 1990, we treated a total of 47 outpatients with advanced tumors using low-dose s.c. rIL-2 and interferon-alpha-2 (rIFN-alpha). Therapy consisted of a 2-day rIL-2 pulse at 18 million IU/m2/day, followed by 6 weeks of rIL-2 (3.6 x 10(6)-4.8 x 10(6) IU/m2/day x 5 days/week) and rIFN-alpha (5 x 10(6)-6 x 10(6) U/m2 x 3/week). Before and after therapy, we phenotypically evaluated circulating lymphocytes and correlated them with clinical response. During 6-week therapy, peripheral blood lymphocytes bearing the CD56 (NK-cell-associated) surface antigen were increased significantly (p < or = 0.005) in treatment responders [complete response (CR) and partial response (PR), n = 10; 3.8-fold] and stable disease (SD) patients (n = 20; 2.1-fold), while patients with progressive disease (PD, n = 17) exhibited no significant expansion of circulating NK cells (p > 0.1). After one 6-week treatment cycle, CR/PR patients had significantly more peripheral NK cells, when compared with patients in SD (1.6-fold) and PD (1.9-fold) (p < 0.04). The overall number of circulating lymphocytes was also increased upon therapy (1.6-fold; p < or = 0.001), but remained independent of response (p > 0.4). These data demonstrate that s.c. rIL-2 and s.c. rIFN-alpha produce a significant increase in peripheral blood NK cells; this expansion correlates significantly with treatment response in advanced tumor patients receiving long-term combination immunotherapy at outpatient doses.

Antigens, CD↗

[Biplane transesophageal echocardiography. Diagnostic improvement over the mono-plane technique].

Monoplane transesophageal echocardiography (TEE) is a well established diagnostic tool of examination of great value in determining pathological changes in both atria, atrioventricular valves, the left-ventricular outflow tract, and in the thoracic aorta (Table 1). With the monoplane technique, however, it is never possible to obtain more than parallel, or oblique transverse views of the heart and surrounding vessels. The only means with which to examine anatomic structures in their cranio-caudal dimension by way of this method is to make a composite of a number of transverse sections. This makes three-dimensional interpretation of monoplane images difficult. The biplane transesophageal technique provides images of orthogonal sections to the transverse plane, allowing three-dimensional reconstruction and thus greatly improved insight into the cardial anatomy. By ante- or retroflection and lateral angulation of the probe, it becomes possible to see structures as a whole, the greatest dimension of which may not lie in the strictly sagittal section, but on a craniocaudal diagonal plane, e.g. the ascending aorta, or the aortic valve plane. The diagnostic gain of additional data through biplane TEE stems from its images of cardial structures, which remain either unsatisfactory or not attainable on monoplane examination (Table 2). Above all this pertains to the superior vena cava in its longitudinal extension (Figure 6), the right-ventricular outflow tract with pulmonary valve, the longitudinal two-chamber view (Figure 3), and the CW-Doppler analysis in presence of tricuspid valve regurgitation (Figure 13). Transversal visualization of the aortic arch is only feasible by using biplane imaging technique (Figure 12). Compared to the monoplane technique, it shows clearly more distinct views of the apex of the left ventricle (Figure 1), the atrial anatomy (Figures 5 and 6), and here in particular the pathology of interatrial septum (Figure 7), as well as the aortic valve and the ascending aorta (Figures 8, 10 and 11). By using the longitudinal imaging plane left atrial appendage can be seen without additional anteflection of the probe, thus, reducing stress to the patient during examination. The loss of an infinite range of planes available to the multiplane technique is a disadvantage, but this can usually be compensated by appropriate flecting of the probe and adequate simultaneous lateral angulation. The range of rotation of the probe in the multiplane method allows better three-dimensional imaging of anatomic structures and regurgitant jets than do the mono- and biplane techniques, and comparable data are often only attained under much longer examination with the biplane instrument.(ABSTRACT TRUNCATED AT 400 WORDS)

Echocardiography, Doppler↗

[Cor triatriatum sinistrum--value of pulmonary vein flow in hemodynamic assessment].

We report on two patients (a 52-year-old female and a 32-year-old male) with cor triatriatum sinistrum, both clinically inconspicuous. The former had undergone strenuous athletic training without difficulty for eight years of her youth. In both cases, cor triatriatum sinistrum was found by chance during transthoracic echocardiography undertaken for hypertension. The exact insertion-site of the left atrial membrane only became apparent by using biplane transoesophageal echocardiography. Neither of the patients showed associated cardiac malformation. Hemodynamics were evaluated by pulsed waved Doppler analysis of pulmonary venous flow profile; no signs of inflow obliteration into the left atrium were found in either case.

Adult↗

[Reversible contact lesion in mitral valve endocarditis--follow-up study with transesophageal echocardiography].

This is a case report of a 59-year-old patient with an endocarditis of the mitral valve caused by streptococcus viridans. Precordial echocardiography showed a highly mobile vegetation of the anterior mitral leaflet prolapsing during systole into the left atrium. During diastole contact with the ventricular septum caudally to the left ventricular outflow tract was noted. By using transesophageal echocardiography (TEE), this zone appeared as a localized increased echogenity of the parietal endocardium and underlying myocardium. Antibiotic therapy led to a cure of the endocarditis (clinically and according to clinical chemistry). The TEE follow-up 2 months later showed persisting mitral valve vegetation, whereas neither the endocardial lesion nor the abnormal myocardial echo pattern were seen any longer. The likely inflammatory etiology of the described lesion is discussed and seems obvious.

Drug Therapy, Combination↗

[Complete visualization of a coronary fistula with drainage into the superior vena cava. Diagnostic benefit of biplane transesophageal echocardiography].

A 36-year-old woman was referred because of a continuous cardiac murmur. Standard transthoracic two-dimensional echocardiography was normal. Using the transverse plane of biplane transesophageal echocardiography (TEE) a distinct dilatation of the proximal portion of the right coronary artery could be visualized. Morphology and the information from color-coded Doppler echocardiography were consistent with a coronary artery fistula. However, the exact course of the fistula and its drainage could not be seen. Only by using the longitudinal plane of biplane TEE its site of drainage into the vena cava superior could be demonstrated morphologically, as well as by color-coded Doppler imaging.

Adult↗

[Cardiac involvement in the hypereosinophilia syndrome. the importance of echocardiography in the follow-up].

A 51-year-old man and a 39-year-old woman with the hypereosinophilic syndrome developed a restrictive cardiomyopathy in the course of cardiac involvement. Echocardiography demonstrated typical thrombotic obliteration at the apex of both ventricles. Doppler ultrasound showed changes of impaired filling in both ventricles. Glucocorticoid treatment (prednisone, 85 mg daily) had to be drastically reduced (to 10 mg daily) in case 1, because of the development of a Cushing syndrome. The man died 18 months later of advanced heart failure. In the woman the eosinophil count fell after prednisone administration (1 mg/kg daily) and there was no recurrence. But heart failure due to impaired diastolic filling has persisted so that orthotopic cardiac transplantation has been planned.

Adult↗

Pretreatment natural killer antigen density correlates to clinical response in tumor patients receiving long-term subcutaneous recombinant interleukin-2 and recombinant interferon-alpha.

We evaluated density of the natural killer (NK) cell-associated CD56 antigen on circulating NK cells of 47 patients with advanced renal cell carcinoma. Patients received a combination of low-dose subcutaneous recombinant interleukin-2 (rIL-2) and recombinant interferon-alpha (rIFN-alpha) as home therapy. Antigen density of CD56 before therapy was 2.2-fold higher (P < 0.005) in patients who subsequently achieved a complete or partial remission when compared with patients who presented with progressive disease on therapy. After a 6-week treatment cycle, NK cells of treatment responders expressed significantly (2.1-fold; P < 0.005) more CD56 antigens than NK cells in nonresponding patients. These results suggested a potential role of both pre- and posttreatment NK antigen density levels as a biologic correlate to treatment response.

Antigens, CD↗